In the orthotopic liver cancer mouse model constructed by overexpressing OPN in HCC cells, the PLX3397 combination therapy significantly enhanced the therapeutic effect of anti-PD-L1 compared with the control group and the group treated with anti-PD-L1 alone, manifested by a reduced incidence of lung metastasis and prolonged survival period [54]. This evidence concerns the gene SPP1 and hepatocellular carcinoma.